An Integrative Systems Biology Approach Identifies Molecular Signatures Associated with Gallbladder Cancer Pathogenesis

Gallbladder cancer (GBC) has a lower incidence rate among the population relative to other cancer types but is a major contributor to the total number of biliary tract system cancer cases. GBC is distinguished from other malignancies by its high mortality, marked geographical variation and poor prognosis. To date no systemic targeted therapy is available for GBC. The main objective of this study is to determine the molecular signatures correlated with GBC development using integrative systems level approaches. We performed analysis of publicly available transcriptomic data to identify differentially regulated genes and pathways. Differential co-expression network analysis and transcriptional regulatory network analysis was performed to identify hub genes and hub transcription factors (TFs) associated with GBC pathogenesis and progression. Subsequently, we assessed the epithelial-mesenchymal transition (EMT) status of the hub genes using a combination of three scoring methods. The identified hub genes including, CDC6, MAPK15, CCNB2, BIRC7, L3MBTL1 were found to be regulators of cell cycle components which suggested their potential role in GBC pathogenesis and progression.

Epidemiological Evidence of the Recent Surge in MS in Asia and Australia: A Systematic Review

Context: Recently, the incidence and prevalence of multiple sclerosis (MS) have increased drastically in different regions of the world, including Asia. The present study aimed to systematically review the recent MS epidemiology in Asia, New Zealand, and Australia. Methods: A systematic literature search was performed in Medline and Embase databases to retrieve the available studies regarding MS epidemiology in Asia, New Zealand, and Australia. Results: Most of the studies were performed in hospital settings. The female-to-male ratio in the sample populations varied from 1.5:1 in Turkey to 5:1 in Malaysia. The total mean age at the onset of MS varied from the minimum of 28 years in Hong Kong to the maximum of 36 years in the United Arab Emirates. Among 16 pertinent studies in this regard, seven addressed the incidence rate of MS, and 13 addressed the prevalence of the disease. The highest prevalence rate was reported to be respectively 124.2 and 148.06 in Australia and Iran versus 2.73 in Malaysia (06 per 100,000 population), while a higher incidence rate was estimated at 6.88 and 6.7 per 100,000 population in Kuwait and Australia, respectively compared to the lower incidence rate per 100,000 population in China (0.2 in females, 0.12 in males). Conclusions: According to the results, the prevalence of MS has increased in Asia, while the prevalence of MS in this continent is lower compared to the rates reported in Australia, Europe, and North America.

A hajas sejtes leukémia korszerű diagnosztikája és kezelése

Összefoglaló. A hajas sejtes leukémia (HCL) egy indolens lefolyású ritka B-sejtes lymphoma. Diagnosztikájában jellegzetes morfológiai képén túlmenően a sejtek felszínén megtalálható markerek azonosítása áramlási citometriával, valamint a betegségben előforduló specifikus fehérjék immunhisztokémiai detektálása jelenti a rutineljárást. Kiemelt szerepet tölt be a differenciáldiagnosztikában a BRAF V600E mutációjának a kimutatása, melyre ma már számos módszer áll rendelkezésre, mint például az immunhisztokémia, pyroszekvenálás, allélspecifikus PCR vagy a droplet digitalis PCR. A tumorsejtek jelátviteli rendszerében és szabályozásában azonban a BRAF mutációjának következtében kialakuló folyamatos aktivitása mellett egyéb mechanizmusok is szerepet játszhatnak, többek között növekedési faktorok, interleukinek, adhéziós fehérjék vagy éppen mikro-RNS-ek. A patomechanizmus egyre részletesebb megismerése érdekében egyéb daganatokhoz hasonlóan a HCL-ben is aktív kutatások folynak a genetikai háttér feltérképezésére új generációs szekvenálás segítségével. Leírtak már nagy százalékban előforduló mutációkat a CDKN1B-, KLF2- és KMT2C-gének esetében, továbbá egyéb génekben is alacsonyabb előfordulási aránnyal. Genetikailag, sőt klinikai manifesztáció és terápiás válasz alapján is jelentős eltérések láthatóak a klasszikus és variáns HCL-es betegek között, elkülönítésük épp ezért rendkívül fontos. Míg a klasszikus esetben első vonalban alkalmazott purin nukleozid analógok kiemelkedő válaszreakciót képesek kiváltani, a variáns HCL-es betegek gyakran refrakterek a kezelésre, és esetükben a célzott BRAF-gátlók szintén hatástalanok. Számos klinikai kutatás zajlik a jelenleg is alkalmazott terápiás szerek optimalizálása, kombinációban történő alkalmazása, valamint egyéb lymphoid daganatokban alkalmazott gyógyszerek és új támadáspontok ellen tervezett molekuláknak a HCL kezelésébe történő bevonása céljából. Summary. Hairy cell leukemia (HCL) is a rare indolent B-cell malignancy. In addition to characteristic morphology of HCL cells, the identification of the cellular surface markers and the expression of specific proteins by flow cytometry and immunohistochemistry are routine procedure in HCL diagnosis. Detection of BRAF V600E mutation plays key role in differential diagnosis of HCL which can be detected by several novel methods, such as immunohistochemistry, pyrosequencing, allele specific PCR or droplet digital PCR. Beside the BRAF mutation there can be other mechanisms causing constitutive activity in the signaling pathway and regulating the tumor cells such as growth factors, interleukins, adhesion proteins and micro-RNAs as well. Like in other malignancies, in order to clarify the pathomechanism, the genetic background of HCL is also actively investigated by next-generation sequencing. Frequent mutations were described in CDKN1B, KLF2 and KMT2C genes, moreover in other genes with lower incidence rate, as well. Genetically, and even in clinical manifestation and therapeutic response, significant differences can be found between patients with classical and variant HCL. While classical type has outstanding response for the first-line treatment with purine analogues, patients with variant HCL are often refractory to the treatment, and the BRAF inhibitors prove to be ineffective. Therefore, it is really important to distinguish these two entities. Several clinical studies are still in progress for the optimization and application of combining the currently applied therapeutic agents, furthermore other drugs that used in lymphoid malignancies are under investigation. New target molecules are also designed as novel therapeutic opportunity in HCL treatment.

СОСТОЯНИЕ ПРОБЛЕМЫ НАРКОЛОГИЧЕСКИХ РАССТРОЙСТВ В КУРСКОЙ ОБЛАСТИ И СОПРЕДЕЛЬНЫХ ТЕРРИТОРИЯХ В 2014-2019 ГОДАХ

Period 2014-2019 characterized by a certain increase in social instability in Russia, which led to an increase of social risk factors for drug addiction. In the Kursk region, at the same time, there have been changes in the regulation of anti-drug prevention, a large number of specialists have been trained, and a movement of competent volunteers has developed. In this regard, the epidemiological data for 2014-2019 are of particular interest. For the period from 2005 to 2019 the primary incidence of alcohol use disorders in Russia decreased from 147.4 to 48.3, in the Kursk region – from 106 to 53.5 cases per 100 000 population per year. Of the adjacent regions in 2019, a lower incidence rate than in the Kursk region was noted only in the Belgorod region – 39.4 cases per 100,000 population. Primary incidence of disorders associated with the use of narcotic active substances, during 2014-2019 in Russia as a whole decreased from 15 to 9.8, in the Kursk region – from 11.3 to 4 new cases per 100 000 inhabitants per year. In 2019, the detection rate of primary incidence of drug addiction and substance abuse was significantly higher than in the Kursk region in Bryansk and Lipetsk. Despite favorable trends, it was noted that the coronavirus pandemic and the restrictions introduced to combat it can have a significant impact on the risk factors for drug addiction, which requires the adaptation of preventive programs to new conditions.

Integrative systems biology approach identified crucial genes and transcription factors associated with gallbladder cancer pathogenesis

Gallbladder cancer (GBC) has a lower incidence rate among the population relative to other cancer types but majorly contributes to the total cancer cases of the biliary tract system. GBC is distinguished from other malignancies due to its high mortality, marked geographical variation and poor prognosis. To date no systemic targeted therapy is available for GBC. The main objective of this study is to determine the molecular signatures correlated with GBC development using integrative system level approaches. We performed analysis of publicly available transcriptomic data to identify differentially regulated genes and pathways. Co-expression network analysis and differential regulatory network analysis identified hub genes and hub transcription factors (TFs) associated with GBC pathogenesis and progression. We then assessed the epithelial-mesenchymal transition (EMT) status of the hub genes using a combination of three scoring methods. The hub genes such as; CDC6, MAPK15, CCNB2, BIRC7, L3MBTL1 identified are regulators of cell cycle components which suggests that cell cycle regulatory genes are significantly linked to GBC pathogenesis and progression.

The Effect of Temperature on the Incidence Rate of COVID19

In this paper, we exploit random variation of daily temperature in the United States at both state and county level, from March 1st to October 31st 2020, to study if temperature has a significant effect on COVID19 incidence rate. We find that warmer than average days lead to a lower incidence rate, seven days later. A week in which temperature is consistently one standard deviation above the monthly average in all US states causes 17,754 fewer cases at national level, seven days later. Other weather variables do not have a significant and robust effect on the incidence rate. The effect of temperature is heterogeneous over space and time.

Transformation of Salicylic Acid and Its Distribution in Tea Plants (Camellia sinensis) at the Tissue and Subcellular Levels

Salicylic acid (SA) is a well-known immune-related hormone that has been well studied in model plants. However, less attention has been paid to the presence of SA and its derivatives in economic plants, such as tea plants (Camellia sinensis). This study showed that tea plants were rich in SA and responded differently to different pathogens. Feeding experiments in tea tissues further confirmed the transformation of SA into salicylic acid 2-O-β-glucoside (SAG) and methyl salicylate. Nonaqueous fractionation techniques confirmed that SA and SAG were mostly distributed in the cytosol of tea leaves, consistent with distributions in other plant species. Furthermore, the stem epidermis contained more SA than the stem core both in C. sinensis cv. “Jinxuan” (small-leaf species) and “Yinghong No. 9” (large-leaf species). Compared with cv. “Yinghong No. 9”, cv. “Jinxuan” contained more SAG in the stem epidermis, which might explain its lower incidence rate of wilt disease. This information will improve understanding of SA occurrence in tea plants and provide a basis for investigating the relationship between SA and disease resistance in tea plants.

Assessment of Major Reproductive Disorders in Dairy Cattle in and around Bale Robe, Oromia Regional State, Ethiopia

A cross-sectional study by employing a questionnaire survey was conducted to determine the prevalence of major reproductive disorders in dairy cattle and its associated risk factors in and around Bale Robe town from November 2016 to April 2017. Out of 384 dairy cows which were under investigation, 254 (66.15%) had encountered at least one of the reproductive disorders. The major reproductive disorders recorded with high prevalence in the present study included mastitis (20.57%), repeat breeder (17.71%), retained fetal membrane (6.51%), uterine and vaginal prolapse (5.47%), and abortion (4.1%), whereas reproductive problems with lower incidence rate included dystocia, anestrus, hypocalcaemia, uterine discharge, and stillbirth accounting 3.91%, 1.82%, 1.30%, 1.04%, and 0.78%, respectively. The overall incidence of reproductive disorders in this study showed statistical significance ( p < 0.05 ) with respect to body condition, age of the animals, production system, and mating system. However, this finding indicated that occurrence of reproductive problems shows statistical insignificance compared to breed, parity, and hygiene of the farm. The prevalence of reproductive disorders in extensive management system (91.02%) was higher than intensive (64.58%) and semi-intensive (57.61%) management systems and also more in local breed (67.93%) than crossbreed (62.29%). However, the prevalence based on parity was higher in primiparous (71.05%) than pluriparous (64.07%) cows. In general, it is recommended that improvement in management system, proper selection of bull and appropriate timing of AI for breeding system, accurate heat detection, routine and periodical examination of cows, balanced feeding, and hygienic condition should be corrected to minimize the incidence of reproductive health disorders and associated risk factors in the study area.

Incidence, clinical features, and outcomes of COVID-19 in Canada: impact of sex and age

Male sex and older age have been reported to be associated with worse outcomes from COVID-19. It was postulated that estrogens may play a role in reducing the severity of the disease and may therefore offer a treatment option for COVID-19 patients. However, more female cases and deaths from COVID-19 have been recorded in Canada. To determine the potential role of estrogens, we analyzed COVID-19 data from Canada, focusing on the impact of sex and age. Although the overall incidence rate is higher in females than in males, when several high risk groups, including health care workers and long-term care residences, which are predominantly females, were excluded, we found that females had a lower incidence rate than males between the ages of 20s to 70s. Interestingly, this sex-based difference is more evident in females of the reproductive ages (20–49) than in postmenopausal patients (60s or older). Males have significantly higher hospitalization, ICU admission, and case fatality rates; however, a greater difference was observed in the older age groups. Finally, symptom manifestation varied between sexes. Some of the symptoms, which were more frequently observed in patients who recovered than patients who died, were more commonly observed in females of the reproductive age compared to their male counterparts. Since only females of the reproductive age have much higher circulating estrogens than males, these findings suggest that estrogens may play a role in reducing COVID-19 incidence and in the development of symptoms, especially those related to better survival.

Single pill regimen improves persistence and leads lo better clinical outcome compared to identical multi pill combination. Results of START, a German claims data analysis

Background/Introduction The current ESC/ESH-Guidelines for the treatment of arterial hypertension (AH) recommend initiation and escalation of medical treatment using renin–angiotensin–aldosterone system (RAAS) blocker, diuretics (D) and/or calcium channel blockers (CCB). They also recommend a single pill (SP) regimen to improve persistence, to increase blood pressure control and to reduce cardiovascular events. Purpose Data showing an advantage for a SP regimen compared to the identical loose combination (LC) regarding all these parameters in a single study are missing. We report now the results comparing SP with identical LC regarding persistence and cardiovascular outcomes in daily practice. Methods This was a retrospective, non-interventional analysis of an anonymized claims dataset covering patients suffering from cardiovascular diseases insured by the German AOK PLUS public health insurance in the years 2012–2017. Patients at age ≥18 years with an indication for the use of a combination of RAAS-blockers, D and/or CCB as SP or identical LC were followed up for 1 year. After 1:1-Propensity Score Matching (PSM) persistence (defined as redemption of prescription with a lack &gt;60 days) and clinical outcomes were compared using non-parametric tests. Results After PSM, baseline characteristics were comparable between SP and LC groups. Each group included 10,801 patients with valsartan/amlodipine, 1,026 with candesartan/amlodipine, 1,823 with amlodipine/valsartan/hydrochlorothiazide (HCT), and 15,349 with ramipril/amlodipine as SP or identical LC. 8 clinical outcomes were compared for each combination. Persistence to treatment was significant higher in the SP group. In 27 of 32 comparisons a significantly lower Incidence Rate Ratio (IRR) was identified for SP. This was confirmed by time-to-event-analysis. The largest patient group (ramipril/amlodipine) showed a significant lower risk for SP observed for stroke (IRR=0.746; 95% CI 0.627–0.886; p&lt;0.001), transitory ischemic attack (IRR=0.693; 95% CI 0.496–0.963; p=0.023), myocardial infarction (IRR=0.623; 95% CI 0.493–0.784; p&lt;0.001), coronary artery disease (IRR=0.579; 95% CI 0.462–0.723; p&lt;0.001), heart failure (IRR=0.468; 95% CI 0.409–0.534; p&lt;0.001), all cause hospitalization (IRR=0.670; 95% CI 0.652–0.687; p&lt;0.001), cardiovascular hospitalization (IRR=0.596; 95% CI 0.519–0.685; p&lt;0.001), and all cause mortality (IRR=0.526; 95% CI 0.463–0.596; p&lt;0.001) compared to LC. Conclusion A SP regimen improves persistence to medication, reduces cardiovascular events and total mortality compared to identical LC. The results of the START study strongly support the use of a SP concept in the AH medication treatment as recommended by the current ESH/ESC-Guidelines for the treatment of AH. Funding Acknowledgement Type of funding source: None